Novel and unusual deletion-insertion thalassemic mutation in exon 1 of the β-globin gene

• Published in: Human mutation Vol. 8; no. 1; pp. 89 - 92
• Main Authors: Badens, Catherine, Thuret, Isabelle, Michel, Gérard, Krawczak, Mickaël, Mattei, Jean-François, Lena-Russo, Danielle, Labie, Dominique, Elion, Jacques
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 1996
• Subjects: beta-Thalassemia - genetics; Exons; Female; Globins - genetics; Haplotypes; Humans; Infant; Mutagenesis, Insertional; Mutation; Sequence Deletion
• ISSN: 1059-7794; 1098-1004
• DOI: 10.1002/(SICI)1098-1004(1996)8:1<89::AID-HUMU16>3.0.CO;2-N

The beta -thalassemias form a group of inherited diseases characterized by an abnormal globin gene function that results in the total absence ( beta degree -thal) or quantitative reduction ( beta super(+)-thal) of beta -globin production. In recent years, there have been many insights into the molecular basis of beta -thalassemia, leading to the conclusion that a fairly homogenous phenotype can result from a surprisingly large number of various genotypes. More than 150 different mutations have been reported as causing beta -thalassemia (The beta and delta -Thalassemia Repository, 1993). Most of them are point mutations in the region spanning from the promoter to the second exon of the beta -gene, resulting in a decreased mRNA production, abnormal splicing, or non-sense. Few are microdeletions ranging from 1 to 25 nucleotides (nt) or microinsertions of 1 nt causing frameshift or non-sense. beta -thal mutations have emerged under the selective pressure of malaria in the same populations as the other globin gene defects. Thus the simultaneous presence of various abnormal globin genes in a single family is not uncommon. Here, we describe a novel beta degree -thal mutation that is unusual because it corresponds to both deletional and insertional events. It was observed in association with the sickle cell disease gene ( beta super(S)) in a family from Algeria. The propositi are two of 38 beta super(S)/ beta -thal compound heterozygotes living in Southern France and whom we have studied in Marseilles.